Molecular and Genomic Epidemiology of Infections Flashcards
what is Molecular Epidemiology?
A measure of differences that determine
Disease distribution in time and place
Disease transmission
Disease manifestation
Disease progression
What kind of questions can molecular epidemiology answer?
Confirming outbreaks (in the lab/hospital/community/institutions)
Identifying disease risks
(shifts in virulence, Influenza)
what can PCR show?
the presence of a gene in each of the different strains
pathogens can have 2 types of characteristics, what are they?
Functional characteristics
Classical, Serology, Virulence
Genomic characteristic
DNA, RNA
do all mutations affect function?
no
silent mutations
Intragenic (between genes) or synonymous (not altering coding)
non-synonymous mutations
Substitutions causing coding to be altered
corruptive mutations
Deletions or Insertions (disrupting coding frame)
Creation or Corruption of STOP codons
Corruption of CONTROL sequences (eg. promoters)
what is meant by drift?
what is meant by antigenic drift?
Gradual alteration in sequence
Antigenic drift is the same antigen changing its sequence base by base
Some mutations have more influence on Ab binding affinity than others
why will a fast replicating organism change quicker than a slower replicating organism?
If bacteria replicates at a really fast rate, each time its making a new genome there are possibility of it making a new one due to mistakes in DNA polymerase
Factors affecting the speed of the ‘Molecular Clock’
Bacterial replication rate
-A high division rate provides a higher mutation rate
DNA or RNA polymerase proof reading ability
-Some species (eg HIV) have low fidelity promoting high mutation rate
Selection pressure from the host or environment
- High selection pressure removes ‘weak’ mutants and emphasises clusters
- Loss of selection pressure allows deletions
Degree of redundancy in the genome
- multiple copies of a single gene in the genome allow for mutations in one copy without compromising overall functionality
- movement or recombination within genome may not effect phenotype
Transmission rate
-High transmission rates relative to the mutation rate
Which genes change the most?
Hyper-variable genes change more rapidly than conserved genes (conserved genes are important for the function of the organism)
BUT conserved genes are more likely to be associated with phenotype and virulence
antigenic shift?
a sudden replacement of an antigen by recombination with another viral type that has evolved separately
gene reassortment
New types will not be protected against by previous infection or vaccination - leading to pandemics
eg. A person with H2 was infected with another strain, H3. The viruses are intracellular and replicate intracellularly. You will get a mix of both – recombination
Molecular typing can aide in?
outbreak sourcing